Abstract
Obesity is a chronic low-grade inflammatory condition in which hypertrophied adipocytes and adipose tissue immune cells, mainly macrophages, contribute to increased circulating levels of proinflammatory cytokines. Obesity-associated chronic low-grade systemic inflammation is considered a focal point and a therapeutic target in insulin resistance and metabolic diseases. We evaluate the effect of Poncirus fructus (PF) on insulin resistance and its mechanism based on inflammatory responses in high-fat diet (HFD)-induced obese mice. Mice were fed an HFD to induce obesity and then administered PF. Body weight, epididymal fat and liver weight, glucose, lipid, insulin, and histologic characteristics were evaluated to determine the effect of PF on insulin resistance by analyzing the proportion of macrophages in epididymal fat and liver and measured inflammatory gene expression. PF administration significantly decreased the fasting and postprandial glucose, fasting insulin, HOMA-IR, total-cholesterol, triglycerides, and low-density lipoprotein cholesterol levels. The epididymal fat tissue and liver showed a significant decrease of fat accumulation in histological analysis. PF significantly reduced the number of adipose tissue macrophages (ATMs), F4/80+ Kupffer cells, and CD68+ Kupffer cells, increased the proportion of M2 phenotype macrophages, and decreased the gene expression of inflammatory cytokines. These results suggest that PF could be used to improve insulin resistance through modulation of macrophage-mediated inflammation and enhance glucose and lipid metabolism.
Highlights
An excess accumulation of body fat resulting from energy imbalance, is a chronic state of low-grade inflammation [1] that is well documented as a contributing factor in the development of diabetes, cardiovascular disease, and non-alcoholic fatty liver disease [2,3]
WBodhyilWeebigohdt aynwd EepiigdhidtymofaltFhaet aPnFd LgirvoeruWpewighatsCrhealnagteisvely low compared to the HFD group (43.14 ± 2.34 g vs. 48.42 ± 3.10 g, respectively), no significant difference in body weight gain was Higher body weight gain was observed in the high-fat diet (HFD) and Poncirus fructus (PF) groups than in the seen (Figureno1rAm)a.l TchhoewH(NFDC) ggrroouupp
We found that PF has favorable effects on hyperglycemia, glucose tolerance, hyperinsulinemia, dyslipidemia, and histopathological fat accumulation in the epididymal fat pad and liver
Summary
An excess accumulation of body fat resulting from energy imbalance, is a chronic state of low-grade inflammation [1] that is well documented as a contributing factor in the development of diabetes, cardiovascular disease, and non-alcoholic fatty liver disease [2,3]. Epididymal fat pad weight compared to the HFD group (2.01 ± 0.10 g vs 2.00 ± 0.25 g, respectively, The PF grouFipgusrheo1wB)e. E2N.1C5 ± 0.10 g, respectivelyg;ropu
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